Formulation and Evaluation of Microcapsules of Aspirin by Coacervation Phase Separation Method

 

Priti B. Savant¹, Shrikrushna A. Shinde², Jayamala S. Barge¹

¹Lecturer, S. R. Institute of Diploma in Pharmacy, Bodhan Nagar, Jalkot Road Udgir - 413517 Maharashtra.

²Principal, S. R. Institute of Diploma in Pharmacy, Bodhan Nagar, Jalkot Road Udgir - 413517 Maharashtra.

 

ABSTRACT:

Microencapsulation is a process in which tiny particles or droplets are surrounded by a coating to give small capsules, with useful properties. Microcapsule is a small sphere with uniform wall around it. The material inside the microcapsule is referred to as the core, internal phase or fill, whereas the wall sometimes called as shell, coating or membrane. Microencapsulation is a rapidly expanding technology in which very tiny droplets or particles of liquid or solid material are surrounded or coated with a continuous film of polymeric material. Aspirin (Acetylsalicylic acid) is a Non steroidal anti-inflammatory drug. It inhibits platelets aggregation and prolong bleeding time. This research article will emphasize formulation and evaluation of microcapsules of aspirin by coacervation phase separation method. coacervation phase separation techanique have been widely used to incorporate drugs into polymeric microcapsules.

 

 

 

INTRODUCTION:

Microencapsulation defined as the packing tools of solids, liquid and gaseous material within the thin polymeric coatings, forming small particles called microencapsulation.

 

Microencapsulation means a method in which tiny droplets of particles such as solid, liquefied or even gas can be coated or surrounded with a polymeric particle. Microcapsule is a small sphere with uniform wall around it. The material inside the microcapsule is referred to as the core, internal phase or fill, whereas the wall sometimes called as shell, coating or membrane.

 

Microencapsulation can also be used to enclose solids, liquids, or gases inside a micrometric wall made of hard or soft soluble film, in order to reduce dosing frequency and prevent the degradation of pharmaceuticals.¹

 

Microencapsulation is a rapidly expanding technology in which very tiny droplets or particles of liquid or solid material are surrounded or coated with a continuous film of polymeric material. The Microencapsulation are involved in converting liquids to solids, which alter colloidal and surface properties, provide environmental protection and control the release characteristics of different coated materials. Most of the microencapsulated product have diameters between 1 to 1000 µm. A large number of core materials like live cells, adhesives, flavors, agrochemicals, enzymes, pharmaceuticals etc., can be encapsulated. The scanning electron microscopy is used to reveal the structural features of microencapsulated compound²

 

The field of cosmetic science holds a bright future for the use of microencapsulation as a delivery system for useful personal care actives. The personal care industry has seen a recent surge in the use of active compounds used to treat skin deficiencies rather than simply masking the problem. As the need for more active compounds increase, the formulation problems increase in proportion to this need. It is a scientific fact that the more active the compound, the more reactive it becomes with the environment in which the compound is placed. This is especially true with respect to typical cosmetic formulations that can be considered harsh environments for active compounds. It is in this arena that the microencapsulation techniques can solve resulting stability issues and deliver the material in an active state to treat the problem areas.

 

Features and benefits of using microencapsulation to enhance personal care formulations include improving aesthetics, protecting the encapsulated compound, improving stability and increasing the shelf life of the finished product, preventing incompatibilities within the formula, controlling the release of the encapsulated compound, and assisting in formulating color cosmetics.³

 

Structures of Microcapsules:

Most microcapsules are small spheres with diameters ranging between a few micrometers and a few millimeters. However, many of these microcapsules bear little resemblance to these simple spheres. In fact, both the size and shape of formed micro particles depend on the materials and methods used to prepare them. The different types of microcapsules and microspheres are produced from a wide range of wall materials like monomers and/or polymers (King, 1995; Shahidi and Han, 1993). Depending on the physicochemical properties of the core, the wall composition and the microencapsulation technique used, different types of particles can be obtained A simple sphere surrounded by a coating of uniform thickness; A particle containing an irregular shape core; Several core particles embedded in a continuous matrix of wall material; Several distinct cores within the same capsule and multi walled microcapsules.⁵

 

Figure-1: Structure and working principle of microencapsulation ⁶

 

HISTORY:

Firstly, in the year 1932, microencapsulation procedure was discovered by Dutch chemist-H.G. Bungenberg de Jong. The first commercial product using the technique of microencapsulation was launched by NCR of American in 1953. The technique of microencapsulation was not a new technology for food processing industry and by the history it was introduced in the mid of 20th century.

 

The terms or materials used in encapsulation process:

The entire microencapsulation is based on terms mainly they are the core material and wall material. The range of micro capsules is from micrometre to millimetre.

·       Core material: The material to be coated is called core material and examples of core materials are solids, liquids or a mixture of these such as dispersion of solids in liquids. Drugs, diluents, stabilizers and rate enhancers can also be core materials.

·       Wall material: The wall material or shell or covering material, the prime function or the objective of wall material is to protect the core material. The examples of wall material are gums, lipids, proteins, carbohydrates, cellulosesetc. The natural examples of core and wall materials are seeds and egg shell respectively

 

Important characteristics of wall material:

The important charactristics of wall material are as follows:

1.     Ability to seal and hold the active material or core material.

2.     Non-reactivity of the coating material with the wall material.

3.     Provide maximum protection to the coating material.

4.     The wall material must be economical and it must be food grade substance.

5.     Approved by controlling authority.

 

Reasons for it is used:

1.     Enhances the overall quality of food products.

2.     Reduces the evaporation or transfer of the core material to the outside environment.

3.     Superior handling of the active agent.

4.     Provides the incorporation of vitamins and minerals.

5.     Improved stability in final product and during processing.

6.     Control release of the active components.

7.     Masks the aroma, flavor, and color of some ingredient

 

Advantages:

1.     Microencapsulation is used in the areas where the drugs are to be delivered to the target sites.

2.     It is also helpful in maintaining the desired concentration at the site of interest without any unwanted effects.

3.     The solid microcapsules have the potential throughout the particle matrix for the controlled and timely release of drugs.

4.     The microcapsules received much attention not only for the prolonged release of drugs but also for targeting the anti-cancer drugs to tumor.⁷

 

Types of Microcapsulation:

Different types of microcapsulation are as follows(show in Figure -2).

      I.   Simple microcapsule

    II.   Matrix (microspore)

 III.   Irregular microscope

 IV.   Multicore microcapsule

   V.   Multiwall microcapsule

 VI.   Assembly of microcapsule

 

Figure-2 : Types of microcapsulation⁸

 

Method of microencapsulation:

1.  Chemical method	Interfacial polymerization, in situ polymerization, piercing-solidifying
2.  Physical-chemical method	Simple coacervation, complex coacervation, phase separation, drying bath, powder bed grinding, melting-dispersion-condensation, capsule-core exchange

 

Coacervation Phase Separation method:

This process consists of three steps

(a)    Formation of three immiscible phases; a liquid manufacturing phase, a core material phase and a coating material phase

(b)    Deposition of the liquid polymer coating on the core material and

(c)    Rigidization of the coating material

 

Step Ist:

Involves the formation of three immiscible chemical phases: a liquid vehicle phase, a coating material phase and a core material phase. The three phases are formed by dispersing the core material in a solution of coating polymer, the vehicle phase is used as a solvent for the polymer. The coating material phase consists of polymer in liquid phase which is formed by using one of the methods of phase separation- coacervation i.e. by changing the temperature of the polymer solution, by adding a solution, or by inducing a polymer- polymer interaction.

 

Figure-3: Coacervation Phase Separation method^9,10

 

Step IInd:

Involves the deposition of the liquid polymer coating upon the core material by controlled mixing of liquid coating material and the core material in the manufacturing vehicle. The liquid coating polymer deposited on the core material if the polymer is adsorbed at the interface formed between the core material and liquid phase. Reduction in the total free interfacial energy of the system help to promote the deposition of the coating material, brought by the decrease of the coating material surface area during coalescence of the liquid polymer droplets. In step III rigidization of the coating material is done by the thermal, cross linking or desolvation technique, to form a selfsupporting microcapsule. (step I st and II nd shown in the Figure no 4)

 

Aim and objective:

·       The main aim for formulation to despite some disadvantages of medication taking in a oral dosage forms which is most popular ways of taking medication.

·       To evaluate prepared aspirin microcapsules

·       To select optimized formulation

 

 

OBJECTIVE:

Microencapsulation drug delivery is the most preferable route of drug delivery due to the ease of administration, patient compliance and flexibility in formulation

 

DRUG AND EXCIPIENT PROFILE:

Chemical Name: Acetylsalicylic Acid

Molecular formula: C₉H₈O₄

Molecular Weight: 180.158 g/mol

IUPAC Name: 2-Acetyloxybenzoic acid

Boiling point: 140 °C

Melting Point: 135 °C

Density: 1.4 g/cm

 

STRUCRTURE:

Structure 1: 3D Structure of Aspirin

 

Structure-2: Aspirin

 

MECHANISM OF ACTION:

The primary mechanism responsible for its anti-inflammatory (reduce inflammation), antipyretic (reduce fever) and analgesic (reduce pain) actions. Aspirin is non-selective and irreversibly inhibits both forms (but is weakly more selective for COX-1). It does so by acetylating the hydroxyl of a serine residue. Normally COX produces prostaglandins, most of which are pro-inflammatory, and thromboxanes, which promote clotting.

 

MEDICAL USES:

Aspirin is used to reduce fever and relieve mild to moderate pain from conditions such as muscle aches, toothaches, common cold, and headaches. It may also be used to reduce pain and swelling in conditions such as arthritis. Aspirin is known as a salicylate and a nonsteroidal anti-inflammatory drug (NSAID). Aspirin can prevent blood clots from forming.

 

ADVERSE EFFECT:

·       Nausea, vomiting, Headache

·       Epigastric distress, peptic ulceration,

·       Gastric mucosal damage.

·       Hypersensitivity

·       Idiosyncrasy

·       Acute salicylate poisoning

 

FORMULATION PROCEDURE:

Material and equipment or Instrument

 

Table-1: Material or Ingredients

 

Table-2: Equipment or Instrument

 

Formulation Table:

Table-3: Ingredient quantity and uses required for formulation

Sr.No	Ingredients.	Quantity (mg)	Uses
1.	Aspirin	3gm	NSAID
2.	Yeast	5gm	Polymer
	Sodium Alginate	5gm	Coating Material
3.	Calcium Chloride	4.8gm	Coating material
4.	Water	Quantity sufficient	Solvent

 

METHOD OF PREPARATION:

Microcapsule is prepared by a coacervation phase separation technique.

 

PROCEDURE:

·         Weighed all the ingredient accurately on weighing balance in the given quantity on the above table.

·         Firstly weighed Sodium alginate and yeast different concentration solutions are prepared by using water.

·         Add sodium alginate in a 10ml water and weighed yeast dissolve 10ml of water

·         In the next step 15% calcium chloride [Cacl₂] solution was set or prepared and kept on magnetic stirrer for uniform mixing and to avoid aggregation of microcapsules.

·       Mix drug properly into two different concentration solutions

·       Mixture of sodium alginate solutions into yeast solution along with drug is prepared.

·       The above solutions, drug and polymer mixture, calcium chloride solution is placed on a magnetic stirrer.

 

Figure-4: Process of Microcapules preparation

 

·       Add slowly drop by drop through syringe having needle size 20 gauge into 15% of calcium chloride (cacl2) solution. Calcium chloride solution is placed on a magnetic stirrer.

·       Microcapsule are prepared then after the preparation microcapsules, these solutions are filtered by using filter paper.

·       Dried the microcapsules in an oven at a room temperature or by air drying for 24 hrs. Dried microcapsules filled in polythene bag.

 

Figure 5: Aspirin Microcapsule

 

Evaluation of Aspirin Microcapsules:

·         Percentage Yield:

The measured weight was divided by total amount of all non‐volatile components which were used for the preparation of microcapsule

 

% yield = (Actual weight of product/Total weight of excipient and drug) x 100

= 2.89gm/10.8gm x 100

= 26.7592

 

·       Microencapsulation efficiency:

From the drug content of microcapsules, microencapsulation efficiency was determined by following formula

 

Microencapsulation efficiency was calculated using the formula:

 

Microencapsulation efficiency =

Estimated % drug content

–––––––––––––––––––––––––––––––– x 10

Theoretical % of drug content

 

·         Incorporation Efficiency:

In 100ml volumetric flask 25mg of crushed microcapsules were taken and dissolved with small quantity of ethanol of the volume is made up to mark with pH 6.8 and stirred for 12 hours. After stirring the solution was filtered through Whatman filter paper and from the filtrate appropriate dilutions were made and absorbance was measured at 206nm by using UV‐ spectrophotometer

 

Table 4: Absorbance readings after several time intervals

 

·         Micromeritic Properties:

Particle Size:

Determination of average particle size of the aspirin microcapsules was carried out by the optical microscopy method. A minute quantity of microcapsules were dispersed in glycerin and then spread on clean glass slide and average sizes inbetween 1 to 1000um of 25 microcapsules were determined in each batch.

 

Angle of Repose:

Determination of angle of repose aspirin microcapsules were carried out by employing fixed funnel method.

 

Angle of repose θ = tan-1 (H/R)

Where,

H = Height of the pile,

R = Radius of the pile

 

Angle of repose = R1+R2+R3/3

= 24.8+21.6+21.6/3 = 22.66

Theta = tan-1 (h/r)

 = tan- 1(2/22.66)

Thete = tan-1(0.001540)

= 1.5574

 

 

 

·         Drug Release:

In vitro release studies:

In vitro dissolution profile of each formulation was determined by employing g USP type 2 basket method (900ml of pH 6.8‐phosphate buffer, 100rpm, 37±0.5O C). Microcapsules equivalent to 100mg of aspirin was loaded into the basket of the dissolution apparatus. 5ml was withdrawn from the dissolution media at suitable time intervals and the withdrawn volume was replenished with the same volume of dissolution medium in order to keep the total volume constant. The absorbance of the samples was measured at λmax 206 nm after suitable dilution if necessary, using phosphate buffer of pH 6.8 as blank. Results of in vitro drug release studies obtained from absorbance data were tabulated and shown graphically as Cumulative % drug released Vs Time.

 

Figure-6: Dissolution of microcapsules

 

RESULT AND DISCUSSION:

Evaluation of preparation

1. Organoleptic Properties

a. Colour = White

b. Odour = Odourless

c. Taste = bitter

 

2. Micromeritic Properties:

a. Particle Size = Inbetween 1 to 1000um

b. Angle of Repose= 1.5574

 

3. Disintegration time= 30 min to 1 hr

4. Dissolution time = 30 min to 1 hr 20min 

 

Table 5: % yield, % encapsulation efficiency, of aspirin microcapsules

Sr. No	% Yield	Encapsulation efficiency
1	26.7592	24.56%
2	30.55	32.54%
3	40.34	41.45%

 

Table 6: Absorbance readings after several time intervals

Sr. No.	Time	Absorbance
1	20 min	0.9179
2	40 min	0.9211
3	60 min	0.9267
4	80 min	0.9305
5	120 min	0.9455

CONCLUSION:

·       Formulating these aspirin microcapsules by coacervation phase separation method is better method is suited to accomplish the coated product  

·       To study to improve of aspirin microencapsulation by utilisation by using std microencapsulation formula.

·       These microcapsules prepared by using coaservation phase separation method two microcapsules must provide or give 400 mg of active ingredient (aspirin) or four microcapsules give 800 mg.

 

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Received on 03.03.2022         Modified on 10.07.2022

Accepted on 09.09.2022   ©AandV Publications All Right Reserved